The main objective of the Epilepsy Research Center (ERC) at the Medical College of Virginia is to establish an integrated and focused research program to improve health care for individuals with epilepsy and to investigate clinical and basic biological mechanisms regulating neuronal excitability and the pathogenesis of seizure disorders. The ERC has developed a consortium of five Jacob Javits Scholars and 28 experienced scientists from diverse disciplines to develop a collaborative program to study the clinical and experimental aspects of epilepsy. A major effort of this integrated research program is directed at studying the pathophysiology of status epilepticus. A unique and rigorously validated status epilepticus data base has been established in the Greater Richmond Metropolitan Area and serves as sa valuable resource for studying mortality, outcome predictors, and serves as a valuable resource for studying mortality, outcome predictors and clinical parameters of this major neurological conditions. Both animal and human studies will investigate the role of microvascular changes and superoxide formation in the pathogenesis of prolonged convulsions. Studies will also probe the role of calcium and a specific anticonvulsant binding protein in the regulation of neuronal excitability and modulation of sustained neuronal discharge. Genetic studies will investigate the genetic basis of some forms of seizures by utilizing one of the largest twin registries in the world. The research projects in the Epilepsy Research Center will test specific hypotheses developed to investigate basic mechanisms and clinical aspects of epilepsy. The component projects will investigate: 1) demographics and epidemiology of status epilepticus; 2) mortality of status epilepticus; 3) microvascular changes and superoxide formation in the pathogenesis of prolonged convulsions; 4) the role of a specific anticonvulsant binding protein in regulating neuronal excitability; 5) calcium modulation of neuronal excitability and seizure discharge; and 6) genetic basis of seizures in twins. The ERC has a clear focus of integrated research projects to understand the clinical and fundamental basis of altered neuronal excitability and seizure discharge and ultimately to develop strategies to improve the diagnosis and treatment of epilepsy.